1. Field of the Invention
The present invention relates to an automated sample extractor or feeder/inoculator and a removable manual override operator for a vessel or conduit. This vessel or conduit can be a bioreactor or other similar equipment.
2. Description of the Background Art
Development of new or more efficient commercialization of existing products requires faster and more effective methods to measure process variables. This is particularly true in processes which require cell culture and fermentation processes conducted in bioreactors where the accuracy of measurements in the research and development are critical for achieving economic production of high purity and highly refined end products.
Some factors which must be controlled include temperature and pressure. These factors are easily measured by utilizing standard sensors. However, many other factors can be measured only by removing samples for external laboratory analysis. The frequency of sample extraction for testing and measurement, number of tests on each sample and the time constraints on the process vary widely as do the methods and equipment used to obtain the samples.
In most cases, measurement processes for variables do not lend themselves to in-situ measurement by remote sensors directly in the process. Instead, samples must be physically extracted from the process and examined and manipulated outside the vessel or conduit. Before this examination and manipulation process can be carried out, a safe, effective means of sample extraction must be made available. By xe2x80x9csafexe2x80x9d here we mean that the process should remain as unaffected by the act of taking a sample as possible as the sample itself should. Besides being safe and effective, the means of sample removal should also take into consideration that the character of sample material taken from one place is very likely to differ from that taken from another place. Therefore, it is important to provide a means by which sample material can be removed from the vessel from a location where its character correlates well with information being derived from in-situ sensor measurements as well as with the character of the bulk of the process material. As such the means for removing material would best be one that also can be flexibly incorporated new or existing systems such as into existing (angled) ferrules and, at the same time, provide a means of sampling the process in the same area as is sampled by other in-situ measurement sensors.
The prior art provides for removal of sample material but does not provide features that could adequately address issues concerning the quality of the material as a representative sample of the process nor the ability to be effectively incorporated into existing system. Many of the prior art designs do not lend themselves easily to use as a retrofit but, instead, require substantial modification to the system for installation or repositioning. An apparatus should minimize or eliminate the dangers associated with the sampling process in an efficient and cost effective manner while providing quality, reproducible results in order to be of value for commercial application.
When working with samples, especially hazardous samples, it is necessary to remove or feed/inoculate material without endangering the integrity of the process, subsequently sampled material, the operator or the outside environment. Many prior art devices are unsatisfactory in this area.
Also, some prior art systems are not automated. Therefore, there is potential danger posed by human procedural errors which could easily result in operator and environmental exposure. Accordingly, a need exists for an automatable apparatus with the capacity for independent verification of equipment operation built in.
There is a need for an automated system which offers a quick, easy-to-use means to override the automation apparatus. Sampling is most important in processes of which relatively little is known. The apparatus should be one that is easily incorporated into new and existing systems in one or more places in a cost-effective way, allowing material to be removed or added to the process at multiple points so that the optimal means for monitoring and controlling the process can be established. Once defined, unnecessary or redundant devices should be easily removed from the process without adversely affecting the process but these devices should, ideally also remain intact and unaffected so that they may be readily used again in other process development, monitoring and control applications.
There always is a need to collect unanticipated samples. In providing this means, it is critical that the apparatus should be able to provide essentially identical samples in either case (i.e. manual or automated mode). Furthermore, the materials being sampled themselves are often expensive. Therefore, excessive removal of sample should be avoided.
In the existing art, rotating cams and rotating knobs or handwheels are usually the means employed to open and close sampling valves. These designs require the operator to move their arm or, at least their hand, through a range of motion of 90-180 degrees or more. In the very best conditions this motion will take at least 1.0 second to perform a full cycle (open and close). Since most sample port apertures are 5 mm or more in diameter, it is very likely that 30 ml or more of process material will flow out between the time the valve is opened and closed. Usually the volume of sample required is small, often 50 ml or less.
As a consequence, one of two events occurs. Either a relatively large amount of sample material is wasted or the technician must resort to xe2x80x9cthrottlingxe2x80x9d the valve (partially opening it). Since process material is either valuable, hazardous or there is a need for cleanliness, there is a tendency of technicians to resort to throttling the valve to more carefully and accurately control the flow of sampling material. However, xe2x80x9cthrottlingxe2x80x9d can significantly alter the sample in two important ways.
First, the smaller, more fluid elements of the sample will more easily pass through the constricted opening rather than the larger, more viscous elements. The result is a selective removal, or sieving out, of the larger, more viscous elements from the sample.
Second, those elements that do pass through the crevice will have been subjected to high levels of shear, possibly significantly altering their physical and chemical properties, changing them from the desired representative subsample of process populations and conditions.
An effective means to minimize this effect will require the valve to be opened to a full open position until enough sample is drawn at which time the valve must be rapidly closed. Automated actuation using electromagnetic solenoids or pneumatic actuators which have only two position, xe2x80x9copenxe2x80x9d or xe2x80x9cclosedxe2x80x9d, are much more preferable over xe2x80x9cthrottlingxe2x80x9d or xe2x80x9cpositioningxe2x80x9d actuators.
Likewise, to eliminate sample bias in a manually operated valve, a manual motion which can be rapidly translated into full articulation of the operating rod from fully xe2x80x9cclosedxe2x80x9d to fully xe2x80x9copenedxe2x80x9d and back must be realized. The fastest (articulating) elements in humans, besides the eyes, are the fingers. A xe2x80x9cflickxe2x80x9d or w xe2x80x9csnapxe2x80x9d of the fingers takes a fraction of a second. Since most sample particles are much smaller than the range of motion used in a single flick of a finger, direct coupling of finger motion to actuation of the operating rod of the sampling valve presents an effective solution. Furthermore, because of the relatively small cross sectional area of sampling orifice and the relatively moderate pressures used in most (biological) manufacturing processes, little or no gear reduction will be required to overcome the tension of a xe2x80x9cfail closexe2x80x9d return spring operating on valve operating rod to close and form a seal at the orifice. The mechanism described here can easily and quickly be removably connected to valves with automated mechanisms. When manual sampling is necessary, trigger-action control can provide a more physically and chemically representative subsample of the process with more precise control of sampling volumes with less wasting of material.
When removing or adding material to a process, it is often desirable to maintain the aseptic integrity of the process as well as protect the surrounding environment. As such it is important that material from the previous removal or addition operation not contaminate the environment, the process or the current sample material. Loss of a sample run or contamination of the process can have extremely expensive ramifications. Therefore, it is important to add material or obtain a sample without the procedure causing contamination.
Many prior art devices permit accumulation or pooling of samples or cleansing medium. When the device is first used this may not create a problem; however, upon subsequent runs, the sample material or material added to the process through the device may be contaminated, or at least, diluted.
Additionally in the prior art, technology used for taking samples is generally unsatisfactory for feeding/inoculating the vessel or container.
Accordingly, it is a primary object of the present invention to provide an apparatus for moving flowable material either in an automated or manual fashion into a vessel or conduit (an inoculation apparatus) or to move flowable material from the vessel or conduit (a sample extractor).
It is an object of the present invention to provide an apparatus which can be retrofitted to existing standard tank port holes without requiring equipment modification.
It is the further object of the invention to provide means to retrofit the present invention into existing tanks port holes of different lengths or to be installed in a penetrating configuration, equivalent to other in-situ sensors.
Another object of the present invention is to provide an apparatus which will provide a representative subsample of the process composition which will better correlate with in-situ sensor measurements, even in applications involving heat labile or electrically sensitive materials.
It is a further object of this invention to provide an automated and manual means of sampling the process, the results of either being of equivalent quality and equally being representative of the process.
It is also an object of the invention to provide a means by which manual and automated operators can be added, removed or exchanged from the valve while it is in service and without jeopardizing the aseptic integrity of either the process or the outside environment.
Another object of the invention is to provide a device that has a safety catch so that the valve cannot accidentally be opened.
Furthermore, it is an object of the invention to provide within the same means a way to lock the valve in the open position to facilitate the taking of large volume of samples.
A further object of the apparatus is to provide a means by which samples can be safely and reliably taken automatically without having to worry about injury to someone who could be caught unaware standing near or up against the device when it automatically actuates. A corollary to this is that blockage to the mechanical elements and interference with sample taking is also avoided.
Still another object of the present invention is to eliminate or minimize the dangers of the sampling process such as contamination of the sample, process or surrounding environment.
It is a further object of the present invention to provide an apparatus which will conduct a sampling and maintain the sample in sealed arrangement such that there will be no danger to the sample itself or to the operator, the process and the surrounding environment.
Another object of the present invention is to provide an automatable system to eliminate operator error.
It is the object of the invention to provide means for effectively duplicating automated action in a manual override mechanism.
Yet another object of the present invention is to provide for a built-in verification of proper operation of the apparatus.
Still another object of the present invention is to provide a sample apparatus which avoids contact of the sample with dynamic (sliding or rotating) seals, thereby avoiding potential sites for accumulation of carryover contaminants.
A further object of the present invention is to eliminate the usual static crevice areas which may collect contaminates but yet are inaccessible to cleaning and sterilization agents and thus eliminates areas which might harbor carryover contaminants.
It is a further object of the present invention to avoid dead (stagnant) spaces in the apparatus which would result in samples that are not truly reflective of the process.
Yet another object of the present invention is to avoid obstacles or barriers to free drainage of the samples, not only when the device is installed in portholes with down-sloping or horizontal interior axes of orientation but also even when the device is installed in portholes with positive interior axes of orientation relative to horizontal.
Another object of the present invention is to provide a relationship that relates the diameter of the valve sampling orifice to the angle of orientation of the porthole""s internal axis with horizontal, the porthole""s internal diameter and the length of the porthole""s internal bottom margin, providing a means to design valves to fit in existing portholes while maintaining the capability to be free-draining as does the invention in its latest embodiment.
Still another object of the present invention is to provide a flushing arrangement for the apparatus whereby contaminants and other material will be forced from the system.
Yet a further object of the present invention is to avoid excess process void volume inside the apparatus which would result in sample volume measurement difficulties and material wastage.
Still another object of the present invention is to avoid passive xe2x80x9cbreathingxe2x80x9d between the seals of the apparatus and the outside environment.
Another object of the present invention is to provide an apparatus which can be repeatedly cleaned and/or sterilized in place.
A further object of the invention is to provide a means by which samples can be extracted from within the body of the process closer to where the sensors take their readings rather then at the margins (of vessels or conduits) where samples are taken as when using prior art devices.
It is an additional object of the invention to minimize the amount of thermal and/or electrical exchanged between the apparatus and the process within the vessel or conduit, especially during heat sterilization cycles, even though the device may be installed in a configuration where in the sampling orifice may be positioned well within the body of the process fluid.
Yet another object of the present invention is to provide an apparatus which can easily be removed and quickly disassembled for maintenance, including replacement of worn parts.
A further object of the present invention is to provide an apparatus whose materials are compatible with the sample materials and the process.
Yet another object of the present invention is to provide a low cost apparatus which can effectively carry out sampling or inoculation.
Still another object of the present invention is to provide an apparatus which will be reliable, easy to maintain and low cost.
Another object of the present invention is to provide multiple use capability of the apparatus including feeding/inoculation as well as sampling.
These and other objects of the present invention are fulfilled by providing an apparatus for moving a sample of flowable material through a port in a wall of a vessel or conduit. Thus, this apparatus can either feed in or withdraw materials.
The apparatus comprises a body having an internal cavity with an end wall and an orifice in that end wall. The valve body, walls near the end wall and the endwall, itself, may be at least one of hollow or coated or fabricated of at least one of a thermally or electrically insulating material. The purpose of the hollow, coated or insulating material character being one of isolating the thermal and/or electrical internal valve sterilization and/or operating process from the heat and/or electrically sensitive process material it may (from time to time) come into contact with. Means (a threaded collar or clamp, for example) which is fixed or adjustable in position along the body is provided for coupling the body to the port in the vessel or conduit. Where isolation of the process from the valve components is necessary, a diaphragm valve is positioned within the internal cavity of the body. Where a diaphragm is necessary to isolate the process, it would incorporate a sealing tip to close off the sampling orifice, said sealing tip being connected to and continuos with a flexing diaphragm which can be removably anchored to the valve body so as to isolate the mechanical components and crevices from the process, two embodiments of the diaphragm valve being one with a diaphragm with a (blind) bulbous tip and a rubber bellows with a tubular body and a blunt sealing tip or one with a long shaft with a (blind) blunt sealing tip at one end and a (conical) flexing base at the other. The tip of the diaphragm can be moved to close or open the orifice. The body of the valve is spaced from the interior surfaces of the internal cavity to thereby define a sample cavity. This-sample cavity is communicable with the orifice. A valve operating rod is attached to the blunt sealing tip and is moved by an appropriate drive to open and close the orifice.
The valve operating rod extends out the rear of the valve through a plate attached to the rear wall of the valve. This plate (may) include seals that isolate the valve interior from the outside environment.
A manual valve actuator, including a leverage adjustable trigger mechanism, a safety catch, a secondary return spring with spring tension adjustment and a stroke-limiting backstop, may be removable connected to the valve body and operating rod at the back of the valve. An automated actuator can also be removable added at the same point with the trigger mechanism being removed and, if desired, reattached onto the rear wall of the automated actuator. The valve operation, therefore, can be either manually or automatically driven, the manual method being one of a finger controlled trigger action mechanism while the automated method being one employing a pneumatic, electromagnetic or other acceptable means of actuation. The results in all cases are essentially the same back and forth articulation of the valve operating rod resulting in opening and closing of the valve.
An inlet passage leads to the sample cavity of the body. In some instances where cleaning and sterilizing can be performed through the sampling orifice, the inlet passage may be eliminated. In practice, if it is present, a restriction is that it also unobstructedly drain down to the drain hole and be connected with the internal cavity.
A drainage trough (or channel) formed in the (anterior portion of the) body leads away from the orifice in the sample cavity of the body to some lowest point within the internal cavity from which material may be drained out of the cavity. The bottom of this channel forms a path between the orifice and the drain opening, the path having an angle or angles of declination to it so that, when installed in a ferrule, the angle of declination of the path is always greater than that of the ferrule. The sides and the rear wall of the internal cavity all have unobstructed paths that drain down to the drain opening exiting the valve which, when in combination with the forward drainage trough lead down to the drain opening lowest point in the internal cavity and form a drainage basin with unobstructed drainage capabilities over a wide range of installation angles. This drain trough or channel has a longitudinal axis which is noncoaxial with the longitudinal axis of the portion of the valve body which can be inserted into the porthole.
In one arrangement, steam, air and/or a wash medium can be supplied through the inlet passage, sample cavity and out the drain passage in order to clean the interior of the apparatus. With the tip of the valve moved to open the orifice, the sample can then be extracted from the vessel or conduit through the sample cavity and out the drain passage. This sample will be fed to means for collecting the sample.
When the apparatus is used for feeding or inoculating, material is normally fed through the inlet passage. This diaphragm valve is retracted and the feed or inoculate is forced through the inlet passage, past the diaphragm valve into the vessel or conduit.
In some case only one passage into or out of the valve is necessary in addition to the orifice. In these cases the washing and sterilizing of the valve can be done through the orifice at the beginning and end of the process or, in the case of feeding, by making use of the drain passage by reversing flows as necessary.
If, when the adjustable collar is positioned part way forward along the barrel of the valve and the tip of the valve is flush with the inside wall of the vessel, the collar may be repositioned all the way back on the barrel of the valve and reinserted into the ferrule. Now the secondary o-ring in the valve cap forms the seal with the ferrule and the tip of the valve will protrude beyond the margins of the vessel into the body of the process in a fashion similar to that of in-situ sensors. Since this is the region where the sensors take their readings, taking samples from this area will correlate better with sensor readings. Alternatively there may only be one o-ring groove along the barrel and the valve may always be installed in a protruding fashion or, if the user does not need to remove the device, the barrel may be permanently affixed into the wall of the vessel or conduit in either the flush or protruding fashion, thereby eliminating the need for the o-ring groove and the adjustable collar.
Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.